Whole-genome sequencing coupled to imputation discovers genetic signals for anthropometric traits

Publication type

Journal Article


  1. Ioanna Tachmazidou
  2. Dániel Süveges
  3. Josine L. Min
  4. Graham R. S. Ritchie
  5. Julia Steinberg
  6. Klaudia Walter
  7. Valentina Iotchkova
  8. Jeremy Schwartzentruber
  9. Jie Huang
  10. Yasin Memari
  11. Shane McCarthy
  12. Andrew A. Crawford
  13. Cristina Bombieri
  14. Massimiliano Cocca
  15. Aliki-Eleni Farmaki
  16. Tom R. Gaunt
  17. Pekka Jousilahti
  18. Marjolein N. Kooijman
  19. Benjamin Lehne
  20. Giovanni Malerba
  21. Satu Männistö
  22. Angela Matchan
  23. Carolina Medina-Gomez
  24. Sarah J. Metrustry
  25. Abhishek Nag
  26. Ioanna Ntalla
  27. Lavinia Paternoster
  28. Nigel W. Rayner
  29. Cinzia F. Sala
  30. William R. Scott
  31. Hashem A. Shihab
  32. Lorraine Southam
  33. Beate St. Pourcain
  34. Michela Traglia
  35. Katerina Trajanoska
  36. Gialuigi Zaza
  37. Weihua Zhang
  38. María Soler Artigas
  39. Narinder Bansal
  40. Marianne Benn
  41. Zhongsheng Chen
  42. Petr Danecek
  43. Wei-Yu Lin
  44. Adam Locke
  45. Jian'an Luan
  46. Alisa K. Manning
  47. Antonella Mulas
  48. Carlo Sidore
  49. Anne Tybjaerg-Hansen
  50. Anette Varbo
  51. Magdalena Zoledziewska
  52. Chris Finan
  53. Konstantinos Hatzikotoulas
  54. Audrey E. Hendricks
  55. John P. Kemp
  56. Alireza Moayyeri
  57. Kalliope Panoutsopoulou
  58. Michal Szpak
  59. Scott G. Wilson
  60. Michael Boehnke
  61. Francesco Cucca
  62. Emanuele Di Angelantonio
  63. Claudia Langenberg
  64. Cecilia Lindgren
  65. Mark I. McCarthy
  66. Andrew P. Morris
  67. Børge G. Nordestgaard
  68. Robert A. Scott
  69. Martin D. Tobin
  70. Nicholas J. Wareham
  71. Paul Burton
  72. John C. Chambers
  73. George Davey Smith
  74. George Dedoussis
  75. Janine F. Felix
  76. Oscar H. Franco
  77. Giovanni Gambaro
  78. Paolo Gasparini
  79. Christopher J. Hammond
  80. Albert Hofman
  81. Vincent W. V. Jaddoe
  82. Marcus E. Kleber
  83. Jaspal S. Kooner
  84. Markus Perola
  85. Caroline Relton
  86. Susan M. Ring
  87. Fernando Rivadeneira
  88. Veikko Salomaa
  89. Timothy D. Spector
  90. Oliver Stegle
  91. Daniela Toniolo
  92. André G. Uitterlinden
  93. Inês Barroso
  94. Celia M. T. Greenwood
  95. John R. B. Perry
  96. Brian R. Walker
  97. Adam S. Butterworth
  98. Yali Xue
  99. Richard Durbin
  100. Kerrin S. Small
  101. Nicole Soranzo
  102. Nicholas J. Timpson
  103. Eleftheria Zeggini

Publication date

June 1, 2017


Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of twelve anthropometric traits associated with height, body mass and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. Seventy-one percent of signals reside within genes and fine-mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits, and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically-relevant discoveries across the frequency spectrum.

Published in

American Journal of Human Genetics

Volume and page numbers

Volume: 100 , p.865 -884







Open Access

Open Access funded by Wellcome Trust

Under a Creative Commons license



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